Alteration of PBMC transcriptome profile after interaction with multipotent mesenchymal stromal cells under "physiological" hypoxia.

Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O2 level. Here we examined the effects of MSCs on transcriptomic profile of allogeneic phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) after interaction at ambient (20%) or "physiological" hypoxia (5%) O2. As revealed with microarray analysis, PBMC transcriptome at 20% O2 was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O2 220 genes were changed. Most of genes at 20% O2 were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O2 levels. A set of altered genes at hypoxia only was of particular interest. According to Gene Ontology a part of above genes was responsible for adhesion, cell communication, and immune response. At both oxygen concentrations, MSCs demonstrated effective immunosuppression manifested as attenuation of T cell activation and proliferation as well as anti-inflammatory shift of cytokine profile. Thus, MSC-mediated immunosuppression is executed with greater efficacy at a "physiological" hypoxia, since the same result has been achieved through a change in the expression of a fewer genes in target PBMCs.

[Surgical treatment of complex incisional hernia]. / Khirurgicheskoe lechenie patsientov so slozhnoi posleoperatsionnoi ventral'noi gryzhei.

There is no generally accepted incisional hernia classification. To categorize incisional hernias, the European Hernia Society (EHS) proposed their classification based on the measurement of three parameters - location, dimension of hernia gate and recurrence. Unfortunately, this classification does not consider the «loss of the domain¼ of 20% or more, local complications including trophic ulcer or fistula of anterior abdominal wall. Moreover, implantation of mesh after previous hernia repair, obesity and other clinical factors are also not considered. Thus, surgeons have recently allocated patients with complex incisional hernia in a separate group. There is no clear definition of this term. There are no clinical guidelines on the management of patients with these hernias, and the choice of optimal surgical treatment remains individual. The authors present a patient with complex incisional hernia. Surgical strategy is described.

[Surgical treatment of enterocutaneous fistulas in patients with ventral incisional hernia]. / Khirurgicheskoe lechenie naruzhnykh kishechnykh svishchei v posleoperatsionnykh gryzhakh.

OBJECTIVE: To determine the optimal surgical treatment in patients with enterocutaneous fistulas combined with ventral incisional hernia. MATERIAL AND METHODS: There were 24 patients with enterocutaneous fistulas combined with ventral incisional hernia. Enterocutaneous fistula was noted in 19 cases, enteroatmospheric fistula - in 5 patients. RESULTS: Simultaneous fistula closure and abdominal wall repair were performed in 14 patients (mesh repair in 5 cases and local approximation of tissues in 9 cases). Postoperative complications occurred in 8 patients, hernia recurrence in long-term period developed in 7 people. Two-stage closure of abdominal wall defect was carried out in 10 patients. Fistula closure was followed by edge-to-edge anterior abdominal wall repair in 5 cases, skin edges were approximated by interrupted sutures or open wound management was performed. There were no postoperative complications and hernia recurrence in this group. CONCLUSION: Surgical treatment of patients with enterocutaneous fistulas combined with hernia should be performed in two stages, i.e. enterocutaneous fistula closure with subsequent hernia repair.

[Abdominal wall repair after total resection of desmoid fibroma in a patient with diabetes mellitus type 1]. / Rekonstruktsiya perednei bryushnoi stenki posle radikal'noi rezektsii desmoidnoi fibromy na fone sakharnogo diabeta 1-go tipa.

Desmoid fibroma (DF) is a rare connective tissue tumor comprising about 0.03-0.13% of all neoplasms. DF has a low potential for malignant transformation, but it is characterized by aggressive course and unfavorable prognosis. The main contingent of patients consists of women of reproductive age. Despite the nearly two-century history of study, there are certain unsolved problems including endocrine problems associated with this disease. We report a 30-year-old female with DF and diabetes mellitus type 1. Total resection of the affected right rectus abdominis muscle was performed in a single block with aponeurotic sheath and peritoneum after normalization of carbohydrate metabolism. Muscular aponeurotic defect 27�10 cm was closed after separation of abdominal wall structures and implantation of polypropylene prosthesis. There are no X-ray and clinical signs of DF recurrence or postoperative hernia after 8 months.

[Massive localized lymphedema of anterior abdominal wall]. / Massivnaya lokalizovannaya limfedema perednei bryushnoi stenki.

Massive localized lymphedema (MLL) is a rare disease observed in people with morbid obesity. MLL is easily confused with soft tissue sarcoma. Therefore, MLL is sometimes called as pseudosarcoma in the literature. MLL was initially described by G. Farshid and S. Weiss in 1998. However, etiology of MLL is still unknown despite certain relationships with injuries, operations and hypothyroidism. Since the term «MLL¼ was introduced only 20 years ago, there are no reliable statistical data on the prevalence of MLL. According to the World Health Organization data (2016), 13% of the adult world population are obese. Therefore, the risk of MLL is increased in these people. Thigh is the most common site of lesion. Abdominal wall lesion is rare and can cause diagnostic difficulties due to large dimensions and appearance. We report a 50-year-old obese woman with MLL of anterior abdominal wall. She experienced discomfort while walking and sleeping due to giant MLL of anterior abdominal wall that significantly reduced quality of life. Removal of MLL (weight 22160 g) was followed by favorable cosmetic and functional outcome. Analysis of differences between MLL and soft tissue sarcoma in the era of «obesity epidemic¼ is valuable for correct diagnosis and treatment of this rare complication. This report is the first case of MLL, registered in Russia. In our opinion, this is associated with insufficient awareness of physicians about this complication of obesity. We hope our observation will help clinicians to identify and treat this complication.

[Hybrid repair of postoperative ventral hernia]. / Gibridnaia metodika lecheniia posleoperatsionnoi ventral'noi gryzhi.

AIM: To develop new technique of abdominal wall repair for postoperative ventral hernia without disadvantages which are intrinsic for open and laparoscopic surgery. MATERIAL AND METHODS: Combined open and laparoscopic hernia repair was used in 18 patients with postoperative ventral hernia. Open stage provided safe dissection of abdominal adhesions and defect closure by autoplasty, laparoscopic procedure consisted of prosthesis deployment without separation of abdominal wall layers. Two types of composite endoprostheses with anti-adhesive coating were used for abdominal wall repair. RESULTS: There were no cases of recurrence or infectious complications in long-term period (from 3 to 106 months). CONCLUSION: Hybrid repair of postoperative ventral hernia is safe and effective procedure. Further studies are necessary to assess cost-effectiveness ratio of this method in view of expensive composite endoprostheses and laparoscopic supplies.

Evaluation of committed and primitive cord blood progenitors after expansion on adipose stromal cells.

Umbilical cord blood mononuclear fraction is a valuable source of hematopoietic stem and progenitor cells (CB HSPCs). The rarity of this population is a serious limitation of its application in cell therapy. Ex vivo expansion enables to significantly amplify the number of hematopoietic precursors of different commitment. Here, we expand CB MNCs in co-culture with human adipose tissue-derived stromal cells (ASCs) to enrich HSPCs and describe phenotypic features of newly formed hematopoietic populations. The CD34+-HSPCs demonstrated 6-fold enrichment with 9000 CFUs per 50 × 103 HSPCs on average. A part of the floating HSPCs were bearing lineage markers, while others were primitive precursors (CD133-/CD34+). Among ASC-associated HSPCs, two subsets of cord blood-borne cells were revealed: СD90+/СD45- and СD90+/СD45+. The proportion of CD3+/CD8+ and NK-T as well as CD25+ and HLA-DR+ Т cells among СD90+/СD45- cells was significantly higher compared to MNCs and floating HSPCs. More than 80% of CD45+/СD90+ HSPCs were identified as late primitive precursors (CD133-/CD34+). Thus, CB MNC expansion in the presence of ASCs provides the generation of both lineage committed lymphoid progenitors and CD34+/CD133- primitive HSPCs. Substantially enriched with primitive precursors, ASC-associated HSPCs could be considered as a perspective tool for a long-term restoration of hematopoiesis in various hematologic disorders.

[Morphological and functional aspects of recurrent postoperative ventral hernias]. / Morfofunktsional'nye aspekty retsidiva posleoperatsionnykh ventral'nykh gryzh.

AIM: To define the optimal treatment of postoperative ventral hernias. MATERIAL AND METHODS: It was performed microscopic examination of intraoperative specimens which were obtained from 40 patients with medium, large and giant hernia. The aim was to reveal ultrastructural changes and morphological features which are associated with abdominal wall weakness in case of postoperative ventral hernia. There were 28 (70%) cases of primary postoperative hernia and 12 (30%) cases of recurrent and multiple-recurrent hernia. In 4 patients polypropylene mesh implants were implanted prior to recurrence. Tissue specimens were obtained from the top of herniation, hernial ring and in 6 cm from the hernial ring. RESULTS AND DISCUSSION: Electron microscopy showed that postoperative ventral hernias are accompanied by ultrastructural destructive changes in cells of the skin, aponeurosis and muscles that indicates on morphofunctional failure of abdominal wall tissues. Swelling and degradation of collagen, fibroblasts vacuolization, capillary sludge of erythrocytes, development of vacuum zones with the fragments of altered collagen fibrils, red blood cells and mast cells are morphological signs of micronecrosis followed by abdominal wall weakness and postoperative ventral hernias. CONCLUSION: Postoperative ventral hernias are associated with morphological and functional failure of abdominal wall due to tissue destructive changes. Therefore, this obviously defective tissue can not be used per se and especially with tension. Mesh implants should be applied.

[Surgical treatment of patients with enteric fistulae].

AIM: To create multidisciplinary diagnostic and curative approach to patients with intestinal fistulae. MATERIAL AND METHODS: Additional nutritive support was applied in all patients preoperatively. 35 patients with intestinal fistulae were operated. Unformed and formed intestinal fistulae were observed in 10 and 25 patients respectively. Radical one-stage surgery was performed in 30 cases, two-stage - in 3 patients. Unformed fistulae opened into granulating wound were not eliminated in 2 patients. RESULTS: Postoperative complications were observed in 10 patients. 2 of them required re-intervention. There were no deaths.